gms | German Medical Science

Aim: TDM helps to maintain optimal drug concentration for viral suppression and to avoid drug toxicity in the management of HIV infection. Compounds with sufficiently long half-lifes in plasma can be monitored at any time between dosing intervals. Single drug levels from routine clinical samples were determined.

Method: Plasma samples obtained from patients with HIV infection, for whom TDM was requested, were evaluated. Samples were either routine samples or were samples obtained in patients encountering specific clinical problems (adverse drug reactions, lack of effect, non-adherence). Plasma values for abacavir, atazanavir, darunavir, efavirenz, emtricitabine, lamivudine, lopinavir, and nevirapine were determined at varying time points between dosing intervals with an assay based on HPLC.

Results: Plasma concentrations of HIV drugs showed a large inter-individual variability. Median and interquartile ranges were calculated and compared to values obtained in clinical trials. Since the nucleoside analogs (NRTI) abacavir, emtricitabine, and lamivudine are metabolized intracellularly to the active moiety, their plasma concentrations do not necessarily represent antiviral activity. However the plasma levels determined were within the normal therapeutic range. On the other hand, for the NNRTI efavirenz and nevirapine suggested minimum target trough concentrations have been published. For efavirenz 76% of the samples were above the suggested minimum therapeutic range of 1µg/ml and for nevirapine 77% of the samples did meet the minimum trough level suggested (3µg/ml). The protease inhibitors (PI) atazanavir, darunavir, and lopinavir are given together with a ritonavir booster and minimum target trough concentrations have been published. The majority of the PI samples analyzed were found to be within the therapeutic plasma level range.

Conclusion: Single measurement TDM of anti-HIV drugs may be sufficient in the routine management of the majority of patients.